This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diabetic retinopathy is a major cause of vision impairment and blindness in working age adults. Discovery of the molecular mechanism on diabetic vision impairment is very critical for further development of healthcare treatments. The retinal pigment epithelial (RPE) cell layer is responsible for maintaining the health of the retina by providing structural and nutritional support largely through gap junctions. Hyperglycemic oxidative stress is the prime-triggering factor for the progress of the disease. RPE cell apoptosis is the primary event for diabetic retinal degeneration. We hypothesize that phytochemicals may act as potential modifiers of the pathology associated with diabetic retinopathy. PKC-gap junctional control of energy homeostasis in the retinal pigment epithelial cell layer is important for healthy vision. We have found that wolfberry extracts have high antioxidant activity in vitro. Application of water soluble wolfberry extracts prevents RPE cells from hyperglycemia/oxidative stress damage by scavenging cellular free radicals. In the current proposal, we will use the whole extracts of Chinese wolfberry, a traditional Chinese herbal medicine, to treat RPE cells in culture and diabetic mice of C57BL/6J (B6) and/or PKC[unreadable] H101Y transgenic in a B6 background. We will determine how wolfberry extracts protect RPE cells from hyperglycemia-induced cell apoptosis through rebalance of cellular energy homeostasis by control of gap junctions. Using these two sets of animal models we will be able to investigate how control of gap junctions by dietary supplements, e.g. addition of wolfberry, protects from cell apoptosis and neuronal degeneration in diabetes in vivo.